Pum2-KO Mouse

Pum2, also known as pumilio 2, is a ribonucleic acid-binding protein. It controls target mRNA turnover, translation, and degradation, thus playing crucial roles in various biological processes [2,3]. It is involved in pathways related to cell proliferation, apoptosis, and phenotypic switching of different cell types, which are relevant to the development of multiple diseases [1,2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying Pum2's functions.

In a murine model of acute ischemic kidney injury, genetic deletion of Mff, whose mRNA translation is negatively regulated by Pum2, attenuated ischemic acute kidney injury-induced renal failure. Overexpression of Pum2 reduced ischemic AKI-mediated Mff upregulation and protected renal tubules [4]. In an Ang-II-induced aortic dissection mouse model, overexpression of Pum2 impeded the development of aortic dissection in vivo, as it inhibited the phenotypic switch of vascular smooth muscle cells (VSMCs) by targeting EFEMP1 mRNA [1]. In a destabilized medial meniscus (DMM) OA mouse model, adenovirus-mediated PUM2 shRNA attenuated OA-induced cartilage damage in vivo, as PUM2 promoted OA progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation [3]. Intestine-specific knockout of Pum2 (along with Pum1) in mice significantly inhibited the progression of colitis-associated cancer in the AOM/DSS model, and knockout or knockdown of Pum2 in human CRC cells decreased tumorigenicity and delayed G1/S transition [5].

In conclusion, Pum2 is a key RNA-binding protein that significantly impacts processes like cell proliferation, apoptosis, and phenotypic switching. Through KO/CKO mouse models, its role in diseases such as acute ischemic kidney injury, aortic dissection, osteoarthritis, and colorectal cancer has been revealed. Understanding Pum2's functions can provide insights into disease mechanisms and potential therapeutic targets.

References:

1. Zhi, Kangkang, Yin, Renqi, Guo, Hongbo, Qu, Lefeng. 2023. PUM2 regulates the formation of thoracic aortic dissection through EFEMP1. In Experimental cell research, 427, 113602. doi:10.1016/j.yexcr.2023.113602. https://pubmed.ncbi.nlm.nih.gov/37062520/

2. Cao, Yuanping, Liu, Caiyun, Wang, Qun, Tao, Ende, Wan, Li. 2020. Pum2 mediates Sirt1 mRNA decay and exacerbates hypoxia/reoxygenation-induced cardiomyocyte apoptosis. In Experimental cell research, 393, 112058. doi:10.1016/j.yexcr.2020.112058. https://pubmed.ncbi.nlm.nih.gov/32437714/

3. Meng, Yu, Chen, Li, Chai, Yuxia, Chen, Juwu, Wang, Nan. 2024. PUM2 promoted osteoarthritis progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation. In Environmental toxicology, 39, 4318-4332. doi:10.1002/tox.24310. https://pubmed.ncbi.nlm.nih.gov/38733337/

4. Wang, Jin, Zhu, Pingjun, Toan, Sam, Ren, Jun, Zhou, Hao. 2020. Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury. In Cell biology and toxicology, 36, 365-378. doi:10.1007/s10565-020-09513-9. https://pubmed.ncbi.nlm.nih.gov/31993882/

5. Gong, Yuanyuan, Liu, Zukai, Yuan, Yihang, Lin, Haifan, Liu, Sanhong. 2022. PUMILIO proteins promote colorectal cancer growth via suppressing p21. In Nature communications, 13, 1627. doi:10.1038/s41467-022-29309-1. https://pubmed.ncbi.nlm.nih.gov/35338151/